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Walter P Maksymowych

Publications and source records attributed to Walter P Maksymowych.

At least 19 recordsLinked to original sources
PubMed2006

Development and validation of a simple tape-based measurement tool for recording cervical rotation in patients with ankylosing spondylitis: comparison with a goniometer-based approach.

OBJECTIVE: To compare a tape-based tool for measuring cervical mobility in patients with ankylosing spondylitis (AS) with the widely practiced goniometer-based approach. METHODS: We developed a novel tape-based approach to measurement of lateral cervical rotation of the neck that is minimally affected by flexion/extension movements of the neck. This requires measurement of the difference between a mark at the suprasternal notch and the tragus of the ear. Rotation score is measured in centimeters and constitutes the difference in length between the 2 extremes of cervical rotation (http://www.arthritisdoctors.org/researcher.html). We assessed the tape-based and goniometer-based methods in a total of 263 patients from 3 countries, Canada (n = 205), Australia (n = 29), and Colombia (n = 29), that included patients from community and tertiary-based practice. Intra- and interobserver reliability was assessed in a subset of 44 patients by ANOVA and a 2-way mixed effects model. The Bath AS Disease Activity (BASDAI) and Function (BASFI) Indices, and the modified Stoke AS Spinal Score (mSASSS), were also recorded to assess construct validity by correlation coefficient and regression analysis. Responsiveness was assessed in a subset of 33 patients that were either randomized to anti-tumor necrosis factor-a therapy:placebo (n = 22) or received open label infliximab (n = 4) or pamidronate (n = 7) over a period of 24 weeks. RESULTS: Scores obtained with the tape-based method were normally distributed, while those obtained using the goniometer were skewed towards normal values. Reliability for the goniometer-based approach was excellent [intraclass correlation coefficient (ICC) > 0.90] and very good for the tape-based approach (ICC > 0.80). Significant correlations were noted between age, disease duration, function and structural damage scores, and scores obtained with both methods. Responsiveness was high using raw scores obtained with the goniometer (standardized response mean > 0.80) but was not evident when the grading scheme proposed for the Bath AS Metrology Index (BASMI) was employed. CONCLUSION: The tape-based approach we describe provides a simple, feasible, and reliable index of cervical rotation that is comparable to the information obtained from the use of a goniometer. If the goniometer-based approach is used, raw scores should be used in the calculation of responsiveness rather than the grading scheme suggested in the BASMI.

Anthropometry↗
PubMed2006

Development and validation of the Edmonton Ankylosing Spondylitis Metrology Index.

OBJECTIVE: Assessment of spinal and hip mobility has been recommended by the Assessments in Ankylosing Spondylitis (AS) Working Group for clinical trials and record keeping, although suggested measures primarily reflect structural damage. Our objective was to validate a simple, 4-item composite measure of spinal and hip mobility, the Edmonton AS Metrology Index (EDASMI). METHODS: We assessed the EDASMI and the Bath AS Metrology Index (BASMI) using a total of 263 patients from 3 countries: Canada (n = 205), Australia (n = 29), and Colombia (n = 29). Intra- and interobserver reliability were assessed in a subset of 44 patients. Construct validity with respect to disease activity (Bath AS Disease Activity Index [BASDAI]), function (Bath AS Functional Index [BASFI]), and structural damage (modified Stoke AS Spinal Score [mSASSS]) was analyzed using correlation and hierarchical regression. Responsiveness was assessed in a subset of 33 patients who received either anti-tumor necrosis factor alpha therapy (n = 26) or pamidronate (n = 7) over 24 weeks. RESULTS: In contrast to the EDASMI, BASMI scores covered a limited range, with 70% of patients demonstrating a score < or =3 (range 0-10) and 4 of 5 individual measures demonstrating substantial floor effects. Both measures were highly reliable (intraclass correlation coefficient >0.90) and demonstrated similar construct validity (EDASMI correlated with disease duration [0.52], BASDAI [0.24], BASFI [0.61], Bath Ankylosing Spondylitis Radiology Index [0.79], mSASSS [0.75]; P < 0.001 for all). The change in EDASMI score was significant after 24 weeks of therapy (standardized response mean 0.40; P = 0.03), but change in the BASMI was not significant. CONCLUSION: The EDASMI is a simple, rapid, and reliable tool for the assessment of spinal mobility in AS that is responsive to therapeutic intervention.

Adult↗
PubMed2006

Does height influence the assessment of spinal and hip mobility measures used in ankylosing spondylitis?

OBJECTIVE: It is not known if height contributes to the variability in mobility measures in patients with ankylosing spondylitis (AS) and whether any measures should be reported corrected for height. We examined the contribution of height to the variability of mobility measures in patients with a diverse spectrum of AS disease. METHODS: We assessed the 9 mobility measures comprising the Bath AS and Edmonton AS Metrology Indices (BASMI and EDASMI) in a total of 205 patients. The contribution of height to the variability in mobility scores was analyzed descriptively according to tertiles of height, and also by combined probability scatter plots that combined each individual's height with the corresponding score for either the composite index or each of the 9 spinal mobility measures. Hierarchical (sequential) linear regression was used to assess the contribution of height to the variance in EDASMI and BASMI composite scores and individual measures, adjusted for age, disease duration, and the Bath AS Disease Activity Index. RESULTS: Descriptive data and correlation analysis revealed significant differences related to height for both the EDASMI and the BASMI, particularly for EDASMI cervical rotation, EDASMI lumbar side flexion, chest expansion, lumbar flexion, and intermalleolar distance. Combined probability scatter plots showed that for a particular height there was a wide distribution of mobility scores and only intermalleolar distance showed some relation to height. Hierarchical regression analysis showed that height contributed significantly, although relatively minimally to the variance of both the EDASMI (3.1%; p <or= 0.05) and the BASMI (3.6%; p <or= 0.05), but only to EDASMI cervical rotation among individual mobility measures (variance of 7.0%; p <or=0.05). CONCLUSION: Body height has minimal effect on the variability of mobility scores in patients with AS. Disease-related factors predominate.

Adult↗
PubMed2006

The role of anti-cyclic citrullinated peptide antibodies in predicting progression of palindromic rheumatism to rheumatoid arthritis.

OBJECTIVE: To determine whether the presence of anti-cyclic citrullinated peptide (anti-CCP) antibodies at presentation is of prognostic value in patients with palindromic arthritis. METHODS: Stored sera, taken around the time of presentation from patients with palindromic arthritis, where available, were assessed for anti-CCP antibodies, and results were correlated with subsequent clinical outcome. RESULTS: Twenty-nine of 61 patients had progressed to rheumatoid arthritis after a mean followup of 5.4 years; 83% of these had had anti-CCP antibodies in their baseline sera. CONCLUSION: The sensitivity/specificity and likelihood ratios for CCP antibodies were better than rheumatoid factor in predicting outcome.

Antibodies, Antinuclear↗
PubMed2006

Educational intervention to reduce falls and fear of falling in patients after fragility fracture: results of a controlled pilot study.

OBJECTIVES: Falls and fear of falling are a major health problem. We sought to determine the effectiveness of an educational intervention in reducing fear of falling and preventing recurrent falls in community-dwelling patients after a fragility fracture. METHODS: One hundred two community-dwelling patients aged 50 years or older who fell and sustained a wrist fracture and were treated at Emergency Departments in Edmonton, Alberta, Canada (2001-2002) were allocated to either standardized educational leaflets and post-discharge telephone counseling regarding fall prevention strategies ("intervention") or attention-controls ("controls"). Main outcomes were fear of falling and recurrent falls 3 months after fracture. RESULTS: Mean age was 67 years and most patients were female (80%). The majority of falls (76%) leading to fracture occurred outdoors. Three months post-fracture, almost half of patients (48%) reported increased fear of falling and 11 of 102 (11%) reported falling again. The intervention did not reduce the fear of falling (43% had increased fear vs. 53% of controls, adjusted P value=0.55) or decrease recurrent falls (17% fell vs. 5% of controls, adjusted P value=0.059) within 3 months of fracture. CONCLUSIONS: An educational intervention undertaken in the Emergency Department was no more effective than usual care in reducing fear of falling or recurrent falls in community-dwelling patients. Future strategies must address a number of dimensions beyond simple education.

Accidental Falls↗
PubMed2006

Prospective observational analysis of the efficacy and safety of low-dose (3 mg/kg) infliximab in ankylosing spondylitis: 4-year followup.

OBJECTIVE: Although there are now compelling data that infliximab is effective for the treatment of AS, most studies have evaluated a dose of 5 mg/kg rather than the 3 mg/kg dose recommended for patients with RA. We assessed the effectiveness and safety of a 3 mg/kg dose of infliximab in normal clinical practice over several years of followup. METHODS: All consecutive patients with AS starting infliximab therapy at 3 mg/kg IV at 0, 2, and 6 weeks and q 2 months between April 2000 and December 2004 were included. Data were systematically collected at baseline, at 14 weeks, and every 6 months thereafter to 4 years or withdrawal. Data included demographic characteristics, Bath AS indices, adverse events, and reasons for withdrawal. Survival taking low-dose infliximab was analyzed by the Kaplan-Meier method with withdrawal for lack of efficacy and/or adverse events and requirement for dose escalation constituting the endpoint. RESULTS: Thirty-four patients (M:F = 26:8), mean age 44.9 years, mean disease duration 17.1 years, and mean BASDAI of 6.4, were studied, of whom 17 had active peripheral synovitis. Median duration of treatment with low-dose infliximab was 1507 days. Fourteen discontinued therapy after a median of 91 days, 6 for adverse events, 6 for lack of efficacy, and 2 were lost to followup. Five (14.7%) patients required dose escalation. Effectiveness demonstrable at 1 year was maintained over 4 years. We did not identify any significant baseline predictors of maintenance on low dose infliximab for > or = 2 years. CONCLUSION: Low-dose (3 mg/kg) infliximab therapy is associated with sustained effectiveness in patients with AS in the real-world setting.

Adult↗
PubMed2006

A randomized, multicenter, double-blind, placebo-controlled phase 2 trial of ISA247 in patients with chronic plaque psoriasis.

BACKGROUND: Use of current oral calcineurin inhibitors for the treatment of psoriasis is limited by toxicity. OBJECTIVE: Evaluate the safety and efficacy of ISA247, a new oral calcineurin inhibitor, in plaque psoriasis patients. METHODS: This 12-week, randomized, double-blind, placebo-controlled, parallel-group study included 201 plaque psoriasis patients with > or = 10% body surface area involvement. Patients were randomized to placebo, ISA247 0.5 mg/kg/d, and ISA247 1.5 mg/kg/d groups. End points included a 2-point reduction in the Static Global Assessment score and a 75% reduction in the Psoriasis Area and Severity Index. RESULTS: A 2-point SGA reduction was achieved in 0% (placebo), 15.6% (0.5 mg/kg/d), and 45.1% (1.5 mg/kg/d) (P < .0001). A 75% reduction in the Psoriasis Area and Severity Index was achieved in 0% (placebo), 18.2% (0.5 mg/kg/d), and 66.7% (1.5 mg/kg/day) (P < .0001). While serum creatinine increased in patients treated with ISA247 1.5 mg/kg/d, it remained within the normal range. LIMITATIONS: Longer-term studies are needed to evaluate the effect of ISA247 on renal function. CONCLUSION: ISA247 appears safe and effective for treating moderate to severe psoriasis.

Adolescent↗
PubMed2006

Association of the IL1 gene cluster with susceptibility to ankylosing spondylitis: an analysis of three Canadian populations.

OBJECTIVE: To examine the association between the IL1 gene cluster and susceptibility to ankylosing spondylitis (AS) in 3 independent case-control cohorts. METHODS: We analyzed 394 patients and 446 controls from Alberta, Newfoundland, and Toronto, Canada. Samples were genotyped using a panel of 38 single-nucleotide polymorphism (SNP) markers within the IL1 gene cluster. Data from 20 informative and nonredundant SNP markers were analyzed using several association test strategies. First, we used the program WHAP to identify single-marker associations. Second, we used WHAP to analyze "sliding windows" of 3 contiguous markers along the entire extent of the IL1 gene cluster in order to identify haplotypic associations. Third, we used the linkage disequilibrium mapping program DMLE to estimate the posterior probability distribution of a disease locus. RESULTS: A total of 14 SNP markers showed significant single-locus disease associations, the most significant being rs3783526 (IL1A) (P = 0.0009 in the Alberta cohort, P = 0.04 in the Newfoundland cohort) and rs1143627 (IL1B) (P = 0.0005 in the Alberta cohort, P = 0.02 in the Newfoundland cohort). Analysis of 3-marker sliding windows revealed significant and consistent associations with all of the haplotypes in the IL1A and IL1B loci in the Alberta cohort and with IL1B in the Newfoundland cohort, especially haplotypes rs1143634/rs1143630/rs3917356 and rs1143630/rs3917356/rs3917354 (P = 0.006-0.0001). With DMLE, a strong peak in the probability distribution was estimated near IL1A in both the Alberta and the Newfoundland populations. CONCLUSION: These results indicate that the IL1 locus, or a locus close to IL1, is associated with susceptibility to AS.

Adult↗
PubMed2006

Rheumatoid arthritis association with the FCRL3 -169C polymorphism is restricted to PTPN22 1858T-homozygous individuals in a Canadian population.

OBJECTIVE: Variants in genes encoding the Fc receptor-like 3 (FcRL-3) and the class II major histocompatibility complex (MHC) transactivator proteins have been associated with an increased risk of rheumatoid arthritis (RA) in Japanese and Nordic populations, respectively. The aim of this study was to investigate these associations in a Canadian Caucasian cohort of RA cases and healthy controls. METHODS: A total of 1,187 RA patients and 462 healthy controls were genotyped for FCRL3 and MHC2TA gene variants associated with RA. Epistasis between the FCRL3 -169C and the PTPN22 1858T variants was also examined. RESULTS: An association was detected between RA and both the FCRL3 -169C allele (OR 1.19, P = 0.023) and the homozygous genotype (OR 1.41, P = 0.027), but association of the MHC2TA promoter region variant (-168G) with RA was not replicated. Stratification of the RA cohort by PTPN22 genotypes revealed the FCRL3 risk variant and RA association was stronger in the patient subgroup lacking PTPN22 1858T variants (P = 0.004) and was not detectable in the subgroup with PTPN22 1858T variants (P = 0.52). The PTPN22 association with RA was greater in the absence than in the presence of the FCRL3 -169C allele (P = 0.0008 versus P = 0.001). The PTPN22 1858T variant also increased the risk of autoimmune thyroid disease (AITD) in the RA patients, whereas the FCRL3 risk variant was protective against AITD. CONCLUSION: Our findings support an association of RA with an FCRL3 functional polymorphism and reveal that this association is stronger in the absence of PTPN22 risk genotypes. These findings support a genetic heterogeneity across RA populations, suggesting that both the FCRL3 and PTPN22 genes play roles in RA susceptibility, but in different individuals.

Adult↗
PubMed2006

Imaging in ankylosing spondylitis.

The introduction of symptomatically highly effective anti-tumour necrosis factor alpha therapies for ankylosing spondylitis (AS) has generated interest in the use of imaging to evaluate the potential structure-modifying properties of these agents. Several approaches have been developed to score the plain radiographic abnormalities in AS. Of these, the modified Stoke AS Spinal Score is the most responsive to change, although responsiveness is limited and requires a minimum of 2 years before significant change becomes apparent in patients on standard therapies. Magnetic resonance imaging (MRI) is the most sensitive imaging abnormality, and the advent of fat-suppression imaging allows detection of bone marrow inflammation in the sacroiliac joints as one of the earliest abnormalities in AS. Limited studies have shown that spinal inflammation can be scored reliably using either a system that evaluates the entire spine or a system that limits evaluation to only the most severely affected spinal segments. Both methods also demonstrate excellent responsiveness. The prognostic significance of acute changes on MRI remains unclear. Reliable approaches to the evaluation of chronic changes are yet to be developed. MRI represents a major advance in the diagnostic evaluation of AS.

Humans↗
PubMed2006

Costs and quality of life of patients with ankylosing spondylitis in Canada.

OBJECTIVE: The use of biological agents in the treatment of ankylosing spondylitis (AS) has emphasized the need for information about the current burden of the disease to estimate the cost-effectiveness of these drugs. We investigated resource utilization and utility of patients with AS in Canada. METHODS: A cross-sectional retrospective observational study was performed in a cohort of 545 patients with AS in Alberta, Ontario, British Columbia, and Manitoba. Patients completed a questionnaire asking about their healthcare consumption, out of pocket expenses, work capacity, and need for informal care during the past 3 months. Patients' current functional status and disease activity level was assessed using the Bath AS functional and disease activity indexes (BASFI and BASDAI), and utility was determined using the EQ-5D 5-dimensional health status classification. Descriptive analysis was performed to estimate costs and utility for the sample and by level of disease severity. RESULTS: Patients' mean age was 49.6 years and the mean disease duration was 22.3 years; 64% were male, and 63% of patients in the sample were working. The mean BASDAI score was 4.3 and BASFI 3.6, although 13% of patients in the sample had a BASFI score > or = 7. The mean annual cost per patient is estimated at 9,008 Canadian dollars (SD 17,724 Canadian dollars), and direct healthcare represented 28.9% of these costs. Patients' out of pocket costs represented 33.1%, and lost work capacity accounted for 38%. Costs increased significantly with diminishing physical function and high disease activity, covering a range of 4,000 Canadian dollars to 30,000 Canadian dollars per patient and year. The estimated cost-increase per unit-increase in the BASFI score at values < 5 was around 1,000 Canadian dollars, and more than 5,000 Canadian dollars at values > 7. The mean utility was 0.65 (SD 0.23). Utility was significantly correlated with age, sex, BASFI, and BASDAI, covering a range from 0.87 for patients with BASFI/BASDAI < or = 2 to 0.20 for patients with BASFI/BASDAI > or = 8. On average, utility decreased by 0.075 for each unit-increase in the BASFI. CONCLUSION: All types of costs accelerate steeply with increasing loss of function (BASFI) and disease activity (BASDAI) in patients with AS, while utility decreases significantly. Treatments that control disease activity and maintain patients' function are likely to offset the high cost and low quality of life of severe disease. Our findings provide information on the burden of AS and a baseline for assessing the cost-effectiveness of the new biological agents in this indication.

Canada↗
PubMed2006

The cost-effectiveness of infliximab (Remicade) in the treatment of ankylosing spondylitis in Canada.

OBJECTIVE: To estimate the cost-effectiveness of the treatment of ankylosing spondylitis (AS) with infliximab (Remicade) in Canada over the long term, with both international and Canadian treatment regimens. METHODS: A previously published disease model based on functional capacity and disease activity was adapted to the Canadian setting. Current resource consumption from a cross-sectional bottom-up burden-of-illness study in 545 patients at different levels of severity of AS in 4 Canadian provinces was incorporated into the model. Cost-effectiveness estimates were based on a 3-month placebo-controlled clinical trial with 2-year open extension as well as a 4-year followup study of clinical practice in Canada. In the cost-effectiveness model, patients with insufficient response to treatment at 12 weeks (> or = 50% reduction in Bath Ankylosing Spondylitis Disease Activity Index) discontinue treatment. In view of the long disease duration, simulations over a 30-year timeframe were performed, incorporating disease progression from cohort studies and assumptions about treatment continuation beyond the clinical trial from the trial extension period. Results are presented in Canadian dollars, from the societal and healthcare payer perspectives, with both costs and effects discounted at 5%. RESULTS: Over a 30-year timeframe, with the assumption that patients' disease would remain stable while on treatment, the cost per quality-adjusted life-year (QALY) gained in the societal perspective is $37,491, using the treatment regimen in the clinical trial (5 mg/kg every 6 weeks). Using the dosing regimen of the Canadian study (75% at 3 mg/kg every 8 weeks, 15% at 3 mg/kg every 6 weeks, and 10% at 5 mg/kg every 8 weeks) the cost per QALY is dollar 10,264. Assuming that patients on treatment progress at half the rate of untreated patients, the cost-effectiveness ratios are dollar 45,121 and dollar 13,883, respectively, while the most conservative assumption that progression is the same in both arms, the ratios are dollar 54,137 and dollar 18,712, respectively. The results are sensitive to the dosing regimen adopted, the discontinuation rate, and assumptions concerning disease progression while on treatment. CONCLUSION: Our results indicate that infliximab therapy for patients with active AS would be cost-effective (ranges dollar 10,264-dollar 54,137 per QALY) in a Canadian setting.

Antibodies, Monoclonal↗
PubMed2005

Spondyloarthritis research Consortium of Canada magnetic resonance imaging index for assessment of sacroiliac joint inflammation in ankylosing spondylitis.

OBJECTIVE: To develop a feasible magnetic resonance imaging (MRI)-based scoring system for sacroiliac joint inflammation in patients with ankylosing spondylitis (AS) that requires minimal scan time, does not require contrast enhancement, evaluates lesions separately at each articular surface, and limits the number of sacroiliac images that are scored. METHODS: A scoring method based on the assessment of increased signal denoting bone marrow edema on T2-weighted STIR sequences was used. MRI films were assessed blindly in random order at 2 sites by multiple readers. Intra- and interreader reliability was assessed by intraclass correlation coefficient (ICC); the 24-week response of patients with AS randomized to placebo:infliximab (3:8) was assessed by effect size and standardized response mean. The reliability and responsiveness of the scoring method were compared for STIR and gadolinium diethylenetriaminepentaacetic (Gd-DTPA)-enhanced MRI sequences. RESULTS: We scanned 11 patients with AS with clinically active disease and 11 additional patients randomized to the trial of infliximab therapy. ICC for total sacroiliac joint STIR score ranged from 0.90 to 0.98 (P < 0.00001) and interobserver ICC for combined readers from the 2 sites was 0.84 (P < 0.0001). ICC for change scores was lower for STIR (ICC 0.53) than for Gd-DTPA-enhanced sequences (ICC 0.79). Responsiveness was poor, although fusion was evident in one-third of patients who received treatment (placebo:infliximab) and inflammation scores were low. CONCLUSION: The Spondyloarthritis Research Consortium of Canada MRI index is a feasible and reproducible index for measuring sacroiliac joint inflammation in patients with AS.

Adult↗
PubMed2005

Spondyloarthritis Research Consortium of Canada magnetic resonance imaging index for assessment of spinal inflammation in ankylosing spondylitis.

OBJECTIVE: To develop a feasible magnetic resonance imaging (MRI)-based scoring system for spinal inflammation in patients with spondylarthropathy that requires minimal scan time, does not require contrast enhancement, evaluates the extent of lesions in 3 dimensional planes, and limits the number of vertebral levels that are scored because MRI demonstrates characteristic inflammatory lesions in the spine of patients with ankylosing spondylitis (AS) prior to the development of typical features on plain radiographic. METHODS: Our scoring method was based entirely on the assessment of increased signal denoting bone marrow edema on T2-weighted STIR sequences. Blinded MRI films were assessed in random order at 2 sites by 3 blinded readers at each of the 2 sites (the Universities of Alberta and Toronto). Intra- and interreader reliability was assessed by intraclass correlation coefficient. The 24-week response of patients with AS randomized to infliximab:placebo (8:3) was assessed by effect size and standardized response mean. RESULTS: An initial analysis of all discovertebral units (DVUs) in the spine of 11 patients demonstrated a mean of 3.2 (95% confidence interval 3.2, 5.2) affected units, while limiting the scoring to a maximum of 6 units captured most of the affected units. We scanned 11 patients with AS with clinically active disease and 20 additional patients randomized to a 24-week trial of either infliximab or placebo. Intraobserver reproducibility for the 6-DVU STIR score ranged from 0.93 to 0.98 (P < 0.0001). Interobserver reproducibility of scores by readers from both sites was 0.79 (P < 0.0001) for status score and 0.82 (P < 0.0001) for change score. Analysis of pretreatment and posttreatment scores for all 20 patients randomized to infliximab/placebo showed a large degree of responsiveness (standardized response mean = 0.87). Reproducibility and responsiveness were only slightly improved by using contrast enhancement with gadolinium diethylenetriaminepentaacetic acid. CONCLUSION: The Spondyloarthritis Research Consortium of Canada MRI index is a feasible, reproducible, and responsive index for measuring spinal inflammation in AS.

Adult↗
PubMed2005

Novel therapies for ankylosing spondylitis.

Recent interest in therapeutic developments for ankylosing spondylitis has focused primarily on two anti-tumor necrosis factor-a therapies, infliximab and etanercept, with several reports establishing their efficacy in pivotal phase III trials. Open extension analyses of earlier controlled trials have also shown that efficacy is maintained for at least 3 years, that monotherapy is adequate, and that treatment is well tolerated with few serious infections. Treatment is associated with reduction in sick leave and days spent in hospital. Despite induction of antinuclear antibodies and anti-ds DNA antibodies, clinical sequelae are rare. Reduction in magnetic resonance imaging parameters of inflammation and serologic biomarkers of cartilage turnover suggest that these agents may be disease-modifying though direct evidence from plain radiographic studies is still lacking. Conventional second line therapies typically used in rheumatoid arthritis have also been examined and while leflunomide appears to possess limited efficacy, there may be a case for re-examining the value of methotrexate.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2005

Etanercept exerts beneficial effects on articular cartilage biomarkers of degradation and turnover in patients with ankylosing spondylitis.

OBJECTIVE: Anti-tumor necrosis factor-alpha (TNF-alpha) therapies are not only beneficial for reducing symptoms in rheumatoid arthritis (RA) but also for structural damage visible on plain radiographs and serological biomarkers of articular cartilage damage. It is not known if these therapies also prevent structural damage in ankylosing spondylitis (AS). The low sensitivity to change over time of plain radiographic instruments mandates a search for the effects of these therapies on possible biomarkers of cartilage damage. METHODS: We studied 2 populations of patients with AS: (1) patients recruited to a placebo controlled trial of etanercept in AS for 16 weeks; (2) an observational cohort receiving infliximab for disease refractory to conventional therapy. Clinical (morning stiffness, nocturnal pain, Bath AS Disease Activity Index) and laboratory [erythrocyte sedimentation rate (ESR), C-reactive protein (CRP)] assessments of disease activity were performed at baseline and at either 16 weeks (clinical trial cohort) or at 14 weeks (observational cohort). We measured serum matrix metalloproteinase-1 (MMP-1), MMP-3, human cartilage glycoprotein-39 (YKL-40), and cartilage oligomeric matrix protein by ELISA at the same timepoints. We also measured serum concentrations of 2 novel biomarker epitopes, C2C and 846, by competitive ELISA. The C2C assay detects a neoepitope at the carboxy terminus of the long three-quarter amino-terminal fragment generated following cleavage of type II collagen by collagenases. Aggrecan 846 epitope is a chondroitin sulfate epitope present on intact aggrecan molecules. Both these assays would detect products originating from both hyaline cartilages and intervertebral discs. RESULTS: There was a significant reduction in levels of C2C (p = 0.005) and a significant increase in the 846 epitope (p = 0.01) in patients who received etanercept compared to placebo controls. Changes in C2C correlated significantly with changes in ESR (r = 0.51, p = 0.04) and CRP (r = 0.48, p = 0.048). Significant changes in C2C were not evident in the infliximab observational cohort, although significant reductions were noted in levels of MMP-3 (p = 0.04) and MMP-1 (p = 0.02) at 14 weeks that were not observed in the etanercept group. Analysis of all baseline samples showed a significant correlation between levels of MMP-3 with CRP (r = 0.73, p < 0.0001), and YKL-40 (r = 0.71, p < 0.0001). No correlation was evident at baseline between levels of C2C or 846 epitope and either acute phase reactants or other biomarkers. CONCLUSION: Our data suggest that an anti-TNF-alpha agent, etanercept, may modify cartilage turnover. These include decreased degradation of type II collagen and increased turnover of aggrecan. Additional therapeutic properties of some anti-TNF-alpha agents in AS, such as infliximab, may be related to decreased expression of MMP. Additional studies in larger populations are therefore warranted.

Adult↗
PubMed2005

Application of the OMERACT filter to scoring methods for magnetic resonance imaging of the sacroiliac joints and the spine. Recommendations for a research agenda at OMERACT 7.

Magnetic resolution imaging (MRI) is a promising tool in the assessment of inflammation and structural damage in clinical trials in ankylosing spondylitis (AS). The ASAS/OMERACT MRI in AS working group, a collaborative initiative of rheumatologists and musculoskeletal radiologists with a special interest in this field, collected data on all available scoring methods for both sacroiliac (SI) joints and spine, and tested them with respect to the OMERACT filter. These data were presented together with the technical specifications of all methods at the OMERACT 7 conference. In addition, the results of 2 separate experiments on the inter-reader reliability of scoring methods to assess activity in SI joints, and on the comparison of STIR sequence versus T1 post-gadolinium (Gd) sequence for the spine, were presented. Thereafter, 8 groups discussed these data and proposed a research agenda, each on a different topic. This information was reported back to all participants and a prioritized research agenda was compiled by voting. Research on scoring methods for assessing disease activity, in both the spine and SI joints, was considered most important. Research on assessing structural damage was considered less important. The specific process and results of this initiative are discussed.

Biomedical Research↗